New Type 2 Diabetes Risk Factors Identified

Martin, S. et al | 2021| Estimating the Effect of Liver and Pancreas Volume and Fat Content on Risk of Diabetes: A Mendelian Randomization Study | Diabetes Care | dc211262. https://doi.org/10.2337/dc21-1262

Type 2 diabetes (T2D) is associated with a number of risk factors and now new research, published in Diabetes Care, suggests that increased levels of liver fat and a smaller pancreas volume may also add to a greater risk of developing T2D.

The new study, conducted at Brunel University, used data collected from 32,859 people who underwent an MRI as part of the UK Biobank study. Data from 9358 participants with type 1 diabetes was also collected from various genome-wide association studies.

“People with type 2 diabetes usually have excess fat in their liver and pancreas, the two key organs in the maintenance of the normal level of blood sugar. The genetic analysis we used in this study is the best possible method to test this relationship,” says Dr Yaghootkar. (via MedScape).

OBJECTIVE

Fat content and volume of liver and pancreas are associated with risk of diabetes in observational studies; whether these associations are causal is unknown. We conducted a Mendelian randomization (MR) study to examine causality of such associations.

RESEARCH DESIGN AND METHODS

We used genetic variants associated (P less than 5 × 10−8) with the exposures (liver and pancreas volume and fat content) using MRI scans of UK Biobank participants (n equal to 32 859). We obtained summary-level data for risk of type 1 (9 358 cases) and type 2 (55 005 cases) diabetes from the largest available genome-wide association studies. We performed inverse–variance weighted MR as main analysis and several sensitivity analyses to assess pleiotropy and to exclude variants with potential pleiotropic effects.

RESULTS

Observationally, liver fat and volume were associated with type 2 diabetes (odds ratio per 1 SD higher exposure 2.16 [2.02, 2.31] and 2.11 [1.96, 2.27], respectively). Pancreatic fat was associated with type 2 diabetes (1.42 [1.34, 1.51]) but not type 1 diabetes, and pancreas volume was negatively associated with type 1 diabetes (0.42 [0.36, 0.48]) and type 2 diabetes (0.73 [0.68, 0.78]). MR analysis provided evidence only for a causal role of liver fat and pancreas volume in risk of type 2 diabetes (1.27 [1.08, 1.49] or 27 per cent increased risk and 0.76 [0.62, 0.94] or 24 per cent decreased risk per 1SD, respectively) and no causal associations with type 1 diabetes.

CONCLUSIONS

Our findings assist in understanding the causal role of ectopic fat in the liver and pancreas and of organ volume in the pathophysiology of type 1 and 2 diabetes.

MedScape New Type 2 Diabetes Risk Factors Identified

Estimating the Effect of Liver and Pancreas Volume and Fat Content on Risk of Diabetes: A Mendelian Randomization Study [paper]

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